Does Entresto Cause Cough?
No, Entresto (sacubitril/valsartan) causes significantly less cough than ACE inhibitors and has a similar low incidence of cough compared to ARBs alone. 1
Evidence from Clinical Trials
The FDA label for Entresto clearly demonstrates that cough is less common with sacubitril/valsartan compared to ACE inhibitors:
- In the PARADIGM-HF trial, cough occurred in 9% of patients on Entresto versus 13% on enalapril (an ACE inhibitor) 1
- This represents a 31% lower incidence of cough with Entresto compared to the ACE inhibitor 1
Why the Difference Matters
The mechanism explains this favorable profile:
- ACE inhibitors cause cough in up to 20% of patients by inhibiting kininase, which increases bradykinin levels 2
- ARBs (like the valsartan component of Entresto) do NOT inhibit kininase, resulting in much lower cough rates 2
- Entresto contains valsartan (an ARB) combined with sacubitril (a neprilysin inhibitor), avoiding the kininase pathway that causes ACE inhibitor-related cough 2
Clinical Implications
If a patient develops cough on Entresto, consider these points:
- Cough is common in heart failure patients due to pulmonary edema or smoking-related lung disease—always exclude worsening heart failure first 2
- The cough is more likely due to the underlying heart failure or other causes rather than the medication itself 2
- Unlike ACE inhibitors where cough is a well-established class effect requiring medication change, cough with Entresto is uncommon and should prompt evaluation for other causes 3
Common Pitfall to Avoid
Do not assume all renin-angiotensin system inhibitors cause equal rates of cough. The 2022 ACC/AHA/HFSA guidelines specifically note that ARBs (and by extension Entresto, which contains an ARB) are associated with "a much lower incidence of cough and angioedema than ACE inhibitors" 2. This is precisely why guidelines recommend switching ACE inhibitor-intolerant patients (due to cough) to ARBs or ARNIs like Entresto 2, 3.